title: Screening of patients with maternally transmitted diabetes for mitochondrial gene mutations in the tRNA[Leu(UUR)] region.
abstract: To investigate the prevalence and clinical characteristics of diabetes mellitus caused by mitochondrial gene mutations in the tRNA[Leu(UUR)] region, a known 'hot spot' for pathogenic mutations, we screened 440 diabetic patients with diabetic mothers for 11 mitochondrial gene mutations reported in mitochondrial neuromuscular disorders; nucleotide pairs (np) 3250, 3251, 3252, 3254, 3256, 3260, 3271, 3291, 3302 and 3303 in addition to an A to G transition at np 3243. The dot-blot hybridization method using 32P-labelled sequence-specific oligonucleotides as probes was used. One subject carrying a T to C transition at np 3271 and seven carrying the A to G transition at np 3243 were identified, while none of the other diabetic patients screened had these mutations in the tRNA[Leu(UUR)] region. The patient with the 3271 mutation, a 39-year-old male, had excellent glycaemic control with diet alone and had neither hearing impairment nor symptoms suggesting mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Thus, among patients with maternally transmitted diabetes, the prevalence of the 3271 mutation was approximately one-seventh that of the 3243 mutation, and other mutations are even more rare in the mitochondrial tRNA[Leu(UUR)] region.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsukuda
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Kameoka
authors.forename: N
authors.initials: N
authors.lastname: Osawa
authors.forename: Y
authors.initials: Y
authors.lastname: Goto
authors.forename: H
authors.initials: H
authors.lastname: Katagiri
authors.forename: T
authors.initials: T
authors.lastname: Asano
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Oka
mesh_terms: D000328:Adult; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D004272:DNA, Mitochondrial / Q000235:genetics*; D003920:Diabetes Mellitus / Q000145:classification / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009035:Mothers; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012356:RNA, Transfer, Leu / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu